25.16 : Hypoglycemia and Glucagon

Without prolonged fasting, healthy individuals maintain blood glucose levels above 3.5 mM due to a well-adapted neuroendocrine counterregulatory system that effectively prevents acute hypoglycemia, a potentially life-threatening condition. The primary clinical scenarios for hypoglycemia encompass diabetes treatment, inappropriate production of endogenous insulin or insulin-like substances by tumors, and the use of glucose-lowering agents in non-diabetic individuals. Notably, hypoglycemia in the context of neoplasms predominantly occurs during fasting or the postabsorptive state.

Hypoglycemia can arise as an adverse reaction to various oral therapies, with insulin therapy posing the greatest risk. Factors contributing to hypoglycemia include insulin dose mismatches, increased insulin sensitivity, and concurrent conditions such as adrenal or pituitary insufficiency. This presents a significant risk that must be carefully balanced against the benefits of glucose control, particularly in the elderly population.

The initial response to hypoglycemia involves reducing endogenous insulin secretion, followed by releasing counterregulatory hormones such as epinephrine, norepinephrine, glucagon, growth hormone, and cortisol. Symptoms manifest when plasma glucose levels reach 60-70 mg/dL (3.3-3.9 mM), including sweating, hunger, paresthesias, palpitations, tremors, anxiety, and autonomic symptoms. Severe hypoglycemia can lead to neurological symptoms, seizures, and coma.

In diabetic patients, the glucagon secretory response to hypoglycemia may become deficient over time, increasing the risk of severe hypoglycemia, especially in those with hypoglycemia unawareness and autonomic neuropathy. Home glucose monitoring is crucial in documenting hypoglycemia, enabling timely intervention and management.

Treatment options for hypoglycemia involve the administration of oral glucose, intravenous glucose, or glucagon, particularly when oral intake is not feasible. Glucagon, produced via recombinant DNA technology, interacts with the glucagon GPCR on target cells, activating the Gs-cAMP-PKA pathway. It is prescribed for individuals at risk of severe hypoglycemia and is administered intravenously, intramuscularly, or subcutaneously, with the intramuscular route being preferred in emergencies. Following the initial response to glucagon, patients should consume oral glucose or food to prevent recurrent hypoglycemia.

Overall, the management of hypoglycemia demands a meticulous understanding of its causes, symptoms, and appropriate therapeutic interventions, ensuring the safety and well-being of affected individuals.